We will continue to focus on two experimental approaches that are proving useful in defining the origins of diversity and interrelationships that exist among the heterogeneous-mononuclear phagocytes. We will continue our characterization of bone marrow-derived macrophages (BMDMO) at various stages of growth in regard to ectoenzyme phenotypes, size distribution, certain cell-surface markers, and resistance to herpes simplex virus (HSV). The intrinsic interaction of HSV with BMDMO appears to be different from that with resident peritoneal MO (RES MO). We are developing methodology for molecular characterization of the HSV DNA species in various MO populations that are infected with HSV in order to determine whether the virus genome persists or whether abortive or defective virion production occurs. These studies use new methodology of dot blot hybridization and Southern blot analysis with high specific activity HSV DNA probes. Our present data indicate that HSV enters resident peritoneal MO and is uncoated, but that no viral DNA synthesis occurs. In BMDMO, on the other hand, some viral DNA synthesis occurs, albeit much lower than fully permissive Vero cells, and there is complete cytopathic effect. These differences may be related to maturational differences between these two mononuclear phagocyte populations. Our other experimental approach uses [unreadable]89[unreadable]Sr to destroy bone marrow. We are defining the effects of this treatment on circulating, peritoneal, and splenic cell populations in regard to MO, natural killer and natural cytotoxic cells, and lymphocyte and polymorphonuclear leukocytes. Determination of ectoenzyme phenotypes of various MO using the two experimental approaches has led us to hypotheaize that the RES MO may be a unique population. Research in this next year will probe the mechanisms involved in origin and maintenance of this population. (MB)